Field of the Invention
Embodiments of the present invention relate, in general, to bio-synchronous bioactive agent delivery of a bioactive agent and more particularly to methodology and systems for individualization and optimization of bio-synchronous bioactive agent delivery of a bioactive agent.
Relevant Background
In the field of drug delivery, it is recognized that supplying the drug in a correct temporal pattern is an important attribute of any drug delivery methodology. Controlled release drug delivery systems are intended to improve response to a drug and/or lessen side effects of a drug. The term “controlled release” refers generally to delivery mechanisms that make an active ingredient available to the biological system of a host in a manner that supplies the drug according to a desired temporal pattern. Controlled release drug delivery may be implemented using instantaneous release systems, delayed release systems, and sustained release systems. In most cases, controlled release systems are designed to maintain a sustained plasma level of an active ingredient in a drug within a human or animal host over a period of time.
Instantaneous release refers to systems that make the active ingredient available immediately after administration to the bio-system of the host. Instantaneous release systems include continuous or pulsed intravenous infusion or injections. Such systems provide a great deal of control because administration can be both instantaneously started and stopped and the delivery rate can be controlled with great precision. However, the administration is undesirably invasive as they involve administration via a puncture needle or catheter. ‘Delayed release’ refers to systems in which the active ingredient made available to the host at some time after administration. Such systems include oral as well as injectable drugs in which the active ingredient is coated or encapsulated with a substance that dissolves at a known rate so as to release the active ingredient after the delay. Unfortunately, it is often difficult to control the degradation of the coating or encapsulate after administration and the actual performance will vary from patient to patient. Sustained release generally refers to release of active ingredient such that the level of active ingredient available to the host is maintained at some level over a period of time. Like delayed release systems, sustained release systems are difficult to control and exhibit variability from patient to patient. Due to the adsorption through the gastrointestinal tract, drug concentrations rise quickly in the body when taking a pill, but the decrease is dependent on excretion and metabolism, which cannot be effectively controlled. In addition, the adsorption through the gastrointestinal tract in many cases leads to considerable side effects (such as ulcers), and can severely damage the liver.
Transdermal drug delivery has developed primarily for sustained release of drugs in situations where oral sustained release systems are inadequate. In some cases, drugs cannot be effectively administered orally because the active ingredients are destroyed or altered by the gastrointestinal system. In other cases the drug may be physically or chemically incompatible with the coatings and/or chelating agents used to implement sustained release. In other cases a transdermal delivery system may provide sustained release over a period of days or weeks whereas orally administered drugs may offer sustained performance over only a few hours. A wide variety of active substances can be delivered through transdermal systems so long as the active substance can be provided in a form that can cross the skin barrier.
In most cases transdermal delivery systems are passive, taking the form of a patch that is adhesively attached to the host. The patch includes a quantity of the active substance, along with a suitable carrier if need be, absorbed in a sponge or similar system. Once applied, the active ingredient diffuses into the host through the skin at a rate determined by the concentration of the active substance and the diffusivity of the active substance. However, a variety of physical and chemical processes at the skin/patch boundary affect the delivery rate and may eventually inhibit drug delivery altogether. Active transdermal delivery systems have been developed to help regulate the delivery rate by providing mechanisms to improve drug delivery over time by “pumping” the active ingredient. One such system is described in U.S. Pat. No. 5,370,635 entitled “DEVICE FOR DELIVERING A MEDICAMENT” which describes a system for delivering a medicament and dispensing it to an organism for a relatively long period of time, for example at least a few days. The device can be adapted for positioning on the surface of the skin of a human or possibly an animal body in order to apply a medicament thereto from the outer side thereof.
Conventional transdermal systems circumvent the disadvantages of the adsorption through the gastrointestinal tract, but they do not optimize or tailor the dosing regiment to offset peak symptoms. In addition the constant transdermal delivery of a drug can lead to severe side effects, including debilitating sleep disorders and ever increasing tolerance.
Timed delivery is most often used to maintain a sustained level of a drug in the body. A significant focus of current research in drug delivery has been to determine the influence of a patient's circadian or other biological rhythms on drug efficacy and efficiency. This research demonstrates that certain disease symptoms follow a daily pattern, with peak symptoms at certain times of the day. It has been widely acknowledged that hormones, neurotransmitters and other intra-body compounds are released in different amounts at different times of the day pursuant to daily patterns. The Wall Street Journal reported on May 27, 2003 that “Doctors are increasingly looking at the clock when it comes to prescribing medicine, instructing patients not only to what drug to use but also precisely when to take it. This new approach stems from a growing body of research that demonstrates that certain diseases tend to get worse at certain times of the day. By synchronizing medications with a patient's body clock, many physicians believe that the drugs will work more effectively and with fewer side effects. In some cases, the improvements have been so pronounced that doctors have been able to reduce dosages.” Similarly, American Pharmacy reports, “Circadian physiologic processes alter drug absorption, distribution, metabolism, and excretion. As a result, drug doses need to be adjusted to meet the differing needs of target organs or tissues at various times of the day.”
Recently, an orally administered drug for arthritis treatment has suggested a chrono-therapeutic approach using a delay release system where the delay is scheduled to release the active ingredient at the beginning of an interleukin 6 cascade that is believed to cause early morning stiffness in rheumatoid arthritis patients. By attempting to synchronize the drug delivery with a biological cycle it is believed that low doses may be used to achieve desired results. However, this system does not overcome the limitations of delayed release systems described above. Although it may be possible to meet the requirements of chrono-pharmacology with pills, such an effort requires an enormous amount of discipline by the patient to comply with the treatment regiment. For example, to achieve optimal results, many patients may need to wake up during the night to take their medication.
Currently, patient compliance (taking the proper dosages at the prescribed times) is a critical problem facing caregivers and pharmaceutical firms alike. Studies show that only about half of patients take medications at the times and in the dosages directed by their physician. It is reported that each year, 125,000 deaths and up to 20% of all hospital and nursing home admissions result from patient non-compliance. And it is estimated that non-compliance results in additional healthcare costs in excess of $100 billion per year in United States. These figures are even more pronounced for the elderly. Hence, a need exists for systems and methods that increase patient compliance as well as administration of a variety of drugs.
One successful Chrono-Therapeutic approach involves synchronizing the administration of compounds with the human body's natural circadian rhythms and addiction rhythms to counteract symptoms when they are likely to be at their worst by using an automated transdermal or other drug administration system. As described in U.S. Pat. No. 7,780,981, “Biosynchronous Transdermal Drug Delivery”, a device delivers varying dosages at varying times, pursuant to a pre-programmed dosage profile. This ensures that peak drug concentrations are present in the bloodstream to offset peak disease and/or addiction symptoms arising from variances and fluctuation in the body's natural circadian rhythms.
While the '981 patent is a tremendous advance in transdermal drug application, the determination of an individuals circadian and biologic rhythm can be a challenge. Moreover, for the efficacy of the treatment protocol to be maximized, the delivery of the pharmacology must be aligned with the needs of each individual. As there is a finite and determinable amount of time from the point of delivery of the drug to its effect, the chosen drug would ideally be delivered immediately prior to the onset of a symptom such as an addictive craving. Accordingly identifying, predicting the onset of a symptom, a craving, and its intensity, is a necessary component to effective addiction cessation treatment. Furthermore, once identified these physiologically and psychological demands must be converted to an individualized dosage profile to optimize efficacy.
It is also widely recognized that the physiological characteristics of an illness also have a psychological effect on a patient and, likewise, that a patient's psychological condition can directly impact one's physiological health. Yet treatment protocols often fail to take into account these two closely interrelated aspects of healthcare. It is widely accepted that emotional support offered by help lines or group discussions can assist an individual to overcome the conditions associated with a physical ailment. Nine-step programs and the like have resounding success regarding addictive related conditions yet few such programs are integrated into pharmacological treatment protocols. What is needed therefore is a comprehensive treatment regime that combines a temporally appropriate and biometrically synchronized pharmacological treatment, the ability to monitor a patient's compliance with the treatment plan, and suitable emotional support. These and other challenges of the prior art are addressed by one or more embodiments of the present invention.
Additional advantages and novel features of this invention shall be set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the following specification or may be learned by the practice of the invention. The advantages of the invention may be realized and attained by means of the instrumentalities, combinations, compositions, and methods particularly pointed out in the appended claims.